This invention relates to stem cell, and more particularly to renal stem cells isolated from kidney tissue.
Renal failure, whether arising from an acute or chronic decline in renal function, is a grave condition that can result in substantial or complete failure of the filtration, reabsorption, endocrine, and homeostatic functions of the kidney. It would be highly desirable to obtain cells, e.g., stem cells, capable of developing into cells that could supply some or all of the functions provided by the kidney. Such cells might be capable of producing functional renal cells or regenerating a functioning kidney, in whole or in part. The functional renal cells or regenerated kidney could be implanted into the donor of the stem cells as an autologous transplant or into another patient. Such renal stem cells could be used to construct an artificial kidney from biological and non-biological components. An artificial kidney might be implanted or used ex vivo to replace or supplement renal function.
Stem cells have been identified in adult mouse brain (Clarke et al. 2000 Science 288:1660) and from 3-5 week old mouse skeletal muscle (Gussoni et al. 1999 Nature 401:390). It has also been suggested that most, if not all epithelial tissues, including the kidney, contain stem cells (Slack 2000 Science 287:1431). Indeed, it has been suggested that the nephron may be an xe2x80x9cepithelial structural-proliferativexe2x80x9d unit, analogous to a liver lobule, an acinus of salivary gland, a stomach gland, or an intestinal crypt (Slack 2000 Science 287:1431).
The invention features renal stem cells isolated from kidney tissue, including adult kidney. The stem cells are capable of contributing to the formation of metanephric tubule cells in fetal or adult kidney.
The invention features a composition comprising isolated renal cells that express Flk-1 and do not substantially express Sca-1. The composition can contain a population of cells that express cell surface Flk-1 wherein less than 30%, less than 20%, less than 10%, less than 5%, less than 1%, less than 0.5%, less than 0.1%, less than 0.01% express cell surface Sca-1. Preferably at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99% of the cells in the composition express Flk-1 and do not substantially express Sca-1. Preferably at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99% of the cells in the composition are renal cells. In various embodiments the cells are human cells, the cells contain a transgene, the cells contain a transgene that encodes a therapeutic protein.
The invention also feature a method for isolating renal stem cells, comprising: obtaining isolated kidney cells; and purifying from the isolated kidney cells a population of cells that express Flk-1 and do not substantially express Sca-1. In certain embodiments the isolation step comprising contacting kidney cells with an antibody the selectively binds to Fkl-1.
The invention also feature a method for treating kidney damage in a patient, the method comprising injecting into a damaged kidney of the patient a therapeutically effective amount of renal stem cells that express Flk-1 and do not substantially express Sca-1. In certain embodiments the renal stem cells are derived from the patient or a matched donor.
The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.